Negative symptoms and cognitive impairment are associated with distinct motivational deficits in treatment resistant schizophrenia.

Y Saleh, I Jarratt-Barnham, P Petitet, E Fernandez-Egea, S G Manohar, M Husain
Author Information
  1. Y Saleh: Nuffield Department Clinical Neurosciences, University of Oxford, Level 6, West Wing, John Radcliffe Hospital, Oxford, OX3 9DU, UK. youssuf.saleh@ndcn.ox.ac.uk.
  2. I Jarratt-Barnham: Department of Psychiatry, University of Cambridge, Herchel Smith Building for Brain & Mind Sciences, Forvie Site, Robinson Way, Cambridge, CB2 0SZ, UK. ORCID
  3. P Petitet: Nuffield Department Clinical Neurosciences, University of Oxford, Level 6, West Wing, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
  4. E Fernandez-Egea: Department of Psychiatry, University of Cambridge, Herchel Smith Building for Brain & Mind Sciences, Forvie Site, Robinson Way, Cambridge, CB2 0SZ, UK.
  5. S G Manohar: Nuffield Department Clinical Neurosciences, University of Oxford, Level 6, West Wing, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
  6. M Husain: Nuffield Department Clinical Neurosciences, University of Oxford, Level 6, West Wing, John Radcliffe Hospital, Oxford, OX3 9DU, UK.

Abstract

BACKGROUND: Motivational deficits are a central feature of the negative syndrome in schizophrenia. They have consistently been associated with reduced willingness to expend physical effort in return for monetary rewards on effort based decision making (EBDM) paradigms. Nevertheless, the mechanisms underlying such altered performance are not well characterised, and it remains unclear if they are driven purely by negative symptoms, or also in part by cognitive impairment, antipsychotic treatment or even positive symptoms. Here we investigated the impact of all these factors using a paradigm that has not previously been used to measure EBDM in schizophrenia.
METHODS: Forty treatment resistant schizophrenia (TRS) patients on clozapine and matched controls (N���=���80) completed a well validated EBDM task which offers monetary rewards in return for physical effort. Choice and reaction time data was analysed using logistic regressions, as well as Bayesian hierarchical drift diffusion modelling (HDDM). Behavioural parameters were compared between groups and their association with negative symptoms, cognitive function and serum clozapine levels were assessed.
RESULTS: Overall, TRS patients accepted significantly less offers than controls during effort-based decision making, suggesting they were less motivated. They demonstrated reduced sensitivity to increasing rewards, but surprisingly were also less averse to increasing effort. Despite a positive correlation between negative symptoms and cognitive function in TRS, reward sensitivity was associated only with cognitive performance. In contrast, reduced effort aversion correlated with negative symptom severity. Clozapine levels and positive symptoms were not associated with either behavioural parameter.
CONCLUSION: Motivational deficits in TRS are characterised by both diminished reward sensitivity and reduced effort aversion during EBDM. Cognitive dysfunction and negative symptom severity account for distinct aspects of these behavioural changes, despite positive associations between themselves. Overall, these findings demonstrate that negative symptoms and cognitive impairment have significant independent contributions to EBDM in TRS, thereby opening the possibility of individualised treatment targeting these mechanisms to improve motivation.

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Grants

  1. /Wellcome Trust
  2. 206330/Z/17/Z/Wellcome Trust
  3. MR/W029987/1/Medical Research Council

MeSH Term

Humans
Schizophrenia
Decision Making
Schizophrenia, Treatment-Resistant
Clozapine
Bayes Theorem
Motivation
Cognitive Dysfunction
Reward

Chemicals

Clozapine

Word Cloud

Created with Highcharts 10.0.0negativesymptomseffortcognitiveEBDMTRSschizophreniaassociatedreducedtreatmentpositivedeficitsrewardswellimpairmentlesssensitivityMotivationalphysicalreturnmonetarydecisionmakingmechanismsperformancecharacterisedalsousingresistantpatientsclozapinecontrolsoffersfunctionlevelsOverallincreasingrewardaversionsymptomseveritybehaviouraldistinctBACKGROUND:centralfeaturesyndromeconsistentlywillingnessexpendbasedparadigmsNeverthelessunderlyingalteredremainsuncleardrivenpurelypartantipsychoticeveninvestigatedimpactfactorsparadigmpreviouslyusedmeasureMETHODS:FortymatchedN���=���80completedvalidatedtaskChoicereactiontimedataanalysedlogisticregressionsBayesianhierarchicaldriftdiffusionmodellingHDDMBehaviouralparameterscomparedgroupsassociationserumassessedRESULTS:acceptedsignificantlyeffort-basedsuggestingmotivateddemonstratedsurprisinglyaverseDespitecorrelationcontrastcorrelatedClozapineeitherparameterCONCLUSION:diminishedCognitivedysfunctionaccountaspectschangesdespiteassociationsfindingsdemonstratesignificantindependentcontributionstherebyopeningpossibilityindividualisedtargetingimprovemotivationNegativemotivational

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